p-Toluenesulfonic acid → 2-[3-(2-hydroxy-ethoxy)-5-methoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one

HRID 591859Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:27][CH3:28])[CH:26]=1)[CH:22]=O.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([C:22]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)[CH:24]=[C:25]([O:27][CH3:28])[CH:26]=1

Participants

Conditions

Temperature: 117.5 °C

Procedure

To a solution of 2-amino-4,6-dimethoxy-benzamide (7.50 g, 38.2 mmol) and 3-(2-hydroxy-ethoxy)-5-methoxy-benzaldehyde (7.50 g, 38.2 mmol) in N,N-dimethylacetamide (30 mL) were added NaHSO3 (58.5 wt %, 4.37 g, 42.0 mmol) and p-TSA (0.72 g, 3.8 mmol). The reaction mixture was heated to 115-120° C. for 16 hours, and then cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure, the residue was diluted with water (50 mL), and the solid was filtered, collected and mixed with ether (50 mL), filtered, and dried under vacuum, to give 2-[3-(2-hydroxy-ethoxy)-5-methoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one as a white solid. Yield: 10 g (70%).

Workup

temperaturecooled to room temperature
customN,N-dimethylacetamide was removed under reduced pressure
additionthe residue was diluted with water (50 mL)
filtrationthe solid was filtered
customcollected
additionmixed with ether (50 mL)
filtrationfiltered
customdried under vacuum

Sources & evidence

ORD record: ord-a64fe9e1ae9443d8853afe097cbc930f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238640B2

Reaction notes

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